U.S. patent number 9,364,614 [Application Number 14/405,991] was granted by the patent office on 2016-06-14 for drug delivery device.
This patent grant is currently assigned to SANOFI-AVENTIS DEUTSCHLAND GMBH. The grantee listed for this patent is SANOFI-AVENTIS DEUTSCHLAND GMBH. Invention is credited to Martin Graefe, Richard Guenther, Thomas Nagel, Rene Richter, Robert Witt.
United States Patent |
9,364,614 |
Nagel , et al. |
June 14, 2016 |
Drug delivery device
Abstract
The invention relates to a drug delivery device, comprising: a
case for retaining drug container, the drug container defining a
cavity for containing a drug, wherein a stopper is slidably
disposed within the container so as to displace the drug through a
discharge nozzle on translation in a distal direction, an inner
magnet disposable within the drug container for abutting the
stopper, at least one outer magnet disposed within the case
coaxially with the container and slidable in an axial direction, a
trigger arrangement for advancing the outer magnet in a distal
direction on actuation, wherein the outer magnet and inner magnet
are arranged for magnetically interacting through the drug
container wall such the outer magnet advances the inner magnet on
trigger actuation.
Inventors: |
Nagel; Thomas (Tharandt,
DE), Richter; Rene (Tharandt, DE), Witt;
Robert (Dresden, DE), Guenther; Richard (Dresden,
DE), Graefe; Martin (Pirna, DE) |
Applicant: |
Name |
City |
State |
Country |
Type |
SANOFI-AVENTIS DEUTSCHLAND GMBH |
Frankfurt am Main |
N/A |
DE |
|
|
Assignee: |
SANOFI-AVENTIS DEUTSCHLAND GMBH
(Frankfurt am Main, DE)
|
Family
ID: |
49782301 |
Appl.
No.: |
14/405,991 |
Filed: |
June 25, 2013 |
PCT
Filed: |
June 25, 2013 |
PCT No.: |
PCT/EP2013/063238 |
371(c)(1),(2),(4) Date: |
December 05, 2014 |
PCT
Pub. No.: |
WO2014/001310 |
PCT
Pub. Date: |
January 03, 2014 |
Prior Publication Data
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|
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Document
Identifier |
Publication Date |
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US 20150126940 A1 |
May 7, 2015 |
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Foreign Application Priority Data
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|
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Jun 27, 2012 [EP] |
|
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12173961 |
|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61M
5/31511 (20130101); A61M 5/30 (20130101); A61M
5/24 (20130101) |
Current International
Class: |
A61M
5/24 (20060101); A61M 5/315 (20060101); A61M
5/30 (20060101) |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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201875042 |
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Jun 2011 |
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CN |
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102162499 |
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Aug 2011 |
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CN |
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Other References
International Search Report for Int. App. No. PCT/EP2013/063238,
completed Aug. 2, 2013. cited by applicant.
|
Primary Examiner: Hayman; Imani
Assistant Examiner: Carpenter; William
Attorney, Agent or Firm: McDonnell Boehnen Hulbert &
Berghoff LLP
Claims
The invention claimed is:
1. Drug delivery device, comprising: a drug container, the drug
container defining a cavity for containing a drug, wherein a
stopper is slidably disposed within the container so as to displace
the drug through a discharge nozzle on translation in a distal
direction, a case for retaining the drug container, an inner magnet
disposable within the drug container for abutting the stopper, at
least one outer magnet disposed within the case coaxially with the
container and slidable in an axial direction, a trigger arrangement
for advancing the outer magnet in a distal direction on actuation,
wherein the outer magnet and the inner magnet are arranged for
magnetically interacting through the drug container wall such the
outer magnet advances the inner magnet on trigger actuation,
characterized in that a cord with a low flexibility is arranged
between a proximal face of the inner magnet and the outer magnet so
as to define their relative axial position, and wherein the cord
runs from the inner magnet in the proximal direction through a
deviating point in a proximal rear cover of the case, then back in
the distal direction and through another deviating point in a
distal front cover and again in the proximal direction to the outer
magnet.
2. Drug delivery device according to claim 1, characterized in that
the cord comprises steel and/or polyethylene and/or aramid
fibres.
3. Drug delivery device according to claim 1, characterized in that
a length of the cord is set so as to keep the inner magnet and the
outer magnet away from a rest position of the inner magnet with
respect to the outer magnet.
4. Drug delivery device according to claim 1, characterized in that
the inner magnet and outer magnet are polarized and axially offset
by the cord so as to attract each other.
5. Drug delivery device according to claim 1, characterized in that
the inner magnet and outer magnet are polarized and axially offset
by the cord so as to repel each other.
6. Drug delivery device according to claim 1, characterized in that
a rear cover of the case comprises a container socket arranged to
receive the inner magnet, wherein the container socket is axially
aligned with the drug container.
7. Drug delivery device according to claim 1, characterized in that
a magnet retainer is arranged in the case for retaining the outer
magnet.
8. Drug delivery device according to claim 1, characterized in that
the outer magnet is arranged as a ring magnet.
9. Drug delivery device according to claim 1, characterized in that
the inner magnet is arranged as a cylindrical magnet.
10. Drug delivery device according to claim 1, characterized in
that the trigger arrangement comprises a threaded bolt threaded to
the outer magnet or a magnet retainer, wherein the threaded bolt is
axially translatable within case by a limited distance.
11. Drug delivery device according to claim 10, characterized in
that a mechanical stop is arranged between the threaded bolt and
the case for limiting relative axial translation.
12. Drug delivery device according to claim 10, characterized in
that a dosing handle is attached to the threaded bolt and extends
proximally from the rear cover so as to allow a user to grab,
rotate and press it.
13. Drug delivery device according to claim 1, characterized in
that the discharge nozzle is arranged as an injection needle or a
jet nozzle.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
The present application is a U.S. National Phase Application
pursuant to 35 U.S.C. .sctn.371 of International Application No.
PCT/EP2013/063238 filed Jun. 25, 2013, which claims priority to
European Patent Application No. 12173961.9 filed Jun. 27, 2012. The
entire disclosure contents of these applications are herewith
incorporated by reference into the present application.
TECHNICAL FIELD
The invention relates to a drug delivery device.
BACKGROUND
Conventional drug delivery devices comprise a container defining a
cavity within for retaining a drug, a nozzle, e.g. an injection
needle arranged at a distal end of the container, wherein the
nozzle is in fluid communication with the cavity, and a stopper
with a plunger disposed in the container for displacing the
drug.
US 2006/030816 A1 discloses a method and apparatus for the storage
and transfer of medical material. In one aspect of the invention a
syringe having rodless piston magnetically couples to an actuator
that is positioned along the syringe independent of the rodless
piston. Another aspect contemplates using medical material in a
cartridge that is used to store like an ampoule and transfer like a
syringe.
SUMMARY
It is an object of the present invention to provide an improved
drug delivery device.
The object is achieved by a drug delivery device according to claim
1.
Preferred embodiments of the invention are given in the dependent
claims.
A drug delivery device according to the invention comprises: a case
for retaining a drug container, the drug container defining a
cavity for containing a drug, wherein a stopper is slidably
disposed within the container so as to displace the drug through a
discharge nozzle on translation in a distal direction, an inner
magnet disposable within the drug container for abutting the
stopper, at least one outer magnet disposed within the case
coaxially with the container and slidable in an axial direction, a
trigger arrangement for advancing the outer magnet in a distal
direction on actuation,
wherein the outer magnet and inner magnet are arranged for
magnetically interacting through the drug container wall such the
outer magnet advances the inner magnet on trigger actuation.
Conventional art pen injectors have a piston rod for displacing the
stopper within the drug container. In order to fully empty the drug
container the piston rod must have approximately the length of the
drug container. An overall length of the pen injector is therefore
about twice the length of the piston rod. By contrast, in the drug
delivery device according to the invention, the force for moving
the stopper is not applied inside the drug container but from
outside through the container wall by the interacting outer and
inner magnet. Hence, a conventional piston rod is not required thus
allowing for nearly halving the overall length of the drug delivery
device, which is thus more compact.
In an exemplary embodiment, a cord with a low flexibility (with
respect to its length) is arranged between a proximal face of the
inner magnet and the outer magnet so as to define their relative
axial position. The cord is preferably tear-resistant and strained
by the force between the magnets.
In an exemplary embodiment the cord comprises steel and/or
polyethylene and/or aramid fibres.
In an exemplary embodiment the cord runs from the inner magnet in
the proximal direction through a deviating point in a proximal rear
cover of the case, then back in the distal direction and through
another deviating point in a distal front cover and again in the
proximal direction to the outer magnet. This allows for a compact
arrangement.
In an exemplary embodiment a length of the cord is set so as to
keep the inner magnet and the outer magnet away from a rest
position of the inner magnet with respect to the outer magnet, e.g.
a position in which the attraction between the magnets would cause
no further movement.
This offset from the rest position keeps the cord tight. Due to the
low flexibility of the cord and the magnetic interaction between
the magnets the relative axial offset between the magnets is held
constant. Thus, when the outer magnet is moved by a certain
distance the inner magnet moves by the same distance thus allowing
for high dose accuracy.
In an exemplary embodiment the inner magnet and outer magnet are
polarized and axially offset by the cord so as to attract each
other. However, movement of the magnets is only allowed on
actuation of a trigger. The outer magnet therefore drags the inner
magnet when being moved on trigger actuation.
In another exemplary embodiment the inner magnet and outer magnet
are polarized and axially offset by the cord so as to repel each
other. The outer magnet therefore pushes the inner magnet when
being translated on trigger actuation.
In an exemplary embodiment a rear cover of the case comprises a
container socket arranged to receive the inner magnet, wherein the
container socket is axially aligned with the drug container. The
container socket serves for defining the position of the inner
magnet prior to insertion of a new drug container.
In an exemplary embodiment a magnet retainer is arranged in the
case for retaining the outer magnet. The magnet retainer
facilitates interaction with the trigger arrangement and the cord
and improves longitudinal guiding of the outer magnet.
In an exemplary embodiment the outer magnet is arranged as a ring
magnet. Likewise, a number of outer magnets may be coaxially
arranged around the drug container.
In an exemplary embodiment the inner magnet is arranged as a
cylindrical magnet.
In an exemplary embodiment the trigger arrangement comprises a
threaded bolt threaded to the outer magnet or the magnet retainer,
wherein the threaded bolt is axially translatable within case by a
limited distance. A dose to be delivered by the drug delivery
device may be set by rotating the threaded bolt which consequently
moves in the proximal direction with respect to the outer magnet
depending on the number of rotations and/or angle of rotation and
the pitch of the threaded bolt. Thus, the distance, by which the
threaded bolt can be depressed and hence the distance, by which the
stopper is shifted on depression of the threaded bolt is varied.
Stopper displacement is proportional to the delivered dose.
In an exemplary embodiment a mechanical stop is arranged between
the threaded bolt and the case for limiting relative axial
translation. The limit may be set by a threaded section of the
threaded bolt having a greater diameter than a non-threaded section
or by a respective collar on the threaded bolt with an increased
diameter so that the part with the smaller diameter may pass
through an opening in the case but the greater diameter part may
not.
In an exemplary embodiment a dosing handle is attached to the
threaded bolt and extends proximally from the rear cover so as to
allow a user to grab, rotate and press it. The dosing handle may
also serve as the limit for moving the threaded bolt. A scale
marking may be provided on the case or on the dosing handle for
relating the angle of rotation to the dose to be delivered.
In an exemplary embodiment the discharge nozzle may be arranged as
an injection needle or a jet nozzle.
The term "drug" or "medicament", as used herein, means a
pharmaceutical formulation containing at least one pharmaceutically
active compound,
wherein in one embodiment the pharmaceutically active compound has
a molecular weight up to 1500 Da and/or is a peptide, a protein, a
polysaccharide, a vaccine, a DNA, a RNA, an enzyme, an antibody or
a fragment thereof, a hormone or an oligonucleotide, or a mixture
of the above-mentioned pharmaceutically active compound,
wherein in a further embodiment the pharmaceutically active
compound is useful for the treatment and/or prophylaxis of diabetes
mellitus or complications associated with diabetes mellitus such as
diabetic retinopathy, thromboembolism disorders such as deep vein
or pulmonary thromboembolism, acute coronary syndrome (ACS),
angina, myocardial infarction, cancer, macular degeneration,
inflammation, hay fever, atherosclerosis and/or rheumatoid
arthritis,
wherein in a further embodiment the pharmaceutically active
compound comprises at least one peptide for the treatment and/or
prophylaxis of diabetes mellitus or complications associated with
diabetes mellitus such as diabetic retinopathy,
wherein in a further embodiment the pharmaceutically active
compound comprises at least one human insulin or a human insulin
analogue or derivative, glucagon-like peptide (GLP-1) or an
analogue or derivative thereof, or exendin-3 or exendin-4 or an
analogue or derivative of exendin-3 or exendin-4.
Insulin analogues are for example Gly(A21), Arg(B31), Arg(B32)
human insulin; Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29)
human insulin; Asp(B28) human insulin; human insulin, wherein
proline in position B28 is replaced by Asp, Lys, Leu, Val or Ala
and wherein in position B29 Lys may be replaced by Pro; Ala(B26)
human insulin; Des(B28-B30) human insulin; Des(B27) human insulin
and Des(B30) human insulin.
Insulin derivates are for example B29-N-myristoyl-des(B30) human
insulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl
human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl
LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human
insulin; B30-N-myristoyl-ThrB29LysB30 human insulin;
B30-N-palmitoyl-ThrB29LysB30 human insulin;
B29-N--(N-palmitoyl-Y-glutamyl)-des(B30) human insulin;
B29-N--(N-lithocholyl-Y-glutamyl)-des(B30) human insulin;
B29-N-(.omega.-carboxyheptadecanoyl)-des(B30) human insulin and
B29-N-(.omega.-carboxyheptadecanoyl) human insulin.
Exendin-4 for example means Exendin-4(1-39), a peptide of the
sequence
H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-
-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-P-
ro-Pro-Ser-NH2.
Exendin-4 derivatives are for example selected from the following
list of compounds:
H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2,
H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2,
des Pro36 Exendin-4(1-39),
des Pro36 [Asp28] Exendin-4(1-39),
des Pro36 [IsoAsp28] Exendin-4(1-39),
des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),
des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),
des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),
des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),
des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),
des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39); or
des Pro36 [Asp28] Exendin-4(1-39),
des Pro36 [IsoAsp28] Exendin-4(1-39),
des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),
des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),
des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),
des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),
des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),
des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39),
wherein the group -Lys6-NH2 may be bound to the C-terminus of the
Exendin-4 derivative;
or an Exendin-4 derivative of the sequence
des Pro36 Exendin-4(1-39)-Lys6-NH2 (AVE0010),
H-(Lys)6-des Pro36 [Asp28] Exendin-4(1-39)-Lys6-NH2,
des Asp28 Pro36, Pro37, Pro38Exendin-4(1-39)-NH2,
H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1-39)-NH2,
H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28]
Exendin-4(1-39)-NH2,
des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,
H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28]
Exendin-4(1-39)-(Lys)6-NH2,
H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28]
Exendin-4(1-39)-(Lys)6-NH2,
H-(Lys)6-des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,
H-des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25]
Exendin-4(1-39)-NH2,
H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]
Exendin-4(1-39)-NH2,
H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]
Exendin-4(1-39)-NH2,
des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]
Exendin-4(1-39)-(Lys)6-NH2,
H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]
Exendin-4(1-39)-(Lys)6-NH2,
H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]
Exendin-4(1-39)-(Lys)6-NH2,
H-(Lys)6-des Pro36 [Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2,
des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1-39)-NH2,
H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]
Exendin-4(1-39)-NH2,
H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]
Exendin-4(1-39)-NH2,
des Pro36, Pro37, Pro38 [Met(O)14, Asp28]
Exendin-4(1-39)-(Lys)6-NH2,
H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]
Exendin-4(1-39)-(Lys)6-NH2,
H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28]
Exendin-4(1-39)-(Lys)6-NH2,
H-Lys6-des Pro36 [Met(O)14, Trp(O2)25, Asp28]
Exendin-4(1-39)-Lys6-NH2,
H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25]
Exendin-4(1-39)-NH2,
H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]
Exendin-4(1-39)-NH2,
H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]
Exendin-4(1-39)-NH2,
des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]
Exendin-4(1-39)-(Lys)6-NH2,
H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]
Exendin-4(S1-39)-(Lys)6-NH2,
H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]
Exendin-4(1-39)-(Lys)6-NH2;
or a pharmaceutically acceptable salt or solvate of any one of the
afore-mentioned Exendin-4 derivative.
Hormones are for example hypophysis hormones or hypothalamus
hormones or regulatory active peptides and their antagonists as
listed in Rote Liste, ed. 2008, Chapter 50, such as Gonadotropine
(Follitropin, Lutropin, Choriongonadotropin, Menotropin),
Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin,
Triptorelin, Leuprorelin, Buserelin, Nafarelin, Goserelin.
A polysaccharide is for example a glucosaminoglycane, a hyaluronic
acid, a heparin, a low molecular weight heparin or an ultra low
molecular weight heparin or a derivative thereof, or a sulphated,
e.g. a poly-sulphated form of the above-mentioned polysaccharides,
and/or a pharmaceutically acceptable salt thereof. An example of a
pharmaceutically acceptable salt of a poly-sulphated low molecular
weight heparin is enoxaparin sodium.
Antibodies are globular plasma proteins (.about.150 kDa) that are
also known as immunoglobulins which share a basic structure. As
they have sugar chains added to amino acid residues, they are
glycoproteins. The basic functional unit of each antibody is an
immunoglobulin (Ig) monomer (containing only one Ig unit); secreted
antibodies can also be dimeric with two Ig units as with IgA,
tetrameric with four Ig units like teleost fish IgM, or pentameric
with five Ig units, like mammalian IgM.
The Ig monomer is a "Y"-shaped molecule that consists of four
polypeptide chains; two identical heavy chains and two identical
light chains connected by disulfide bonds between cysteine
residues. Each heavy chain is about 440 amino acids long; each
light chain is about 220 amino acids long. Heavy and light chains
each contain intrachain disulfide bonds which stabilize their
folding. Each chain is composed of structural domains called Ig
domains. These domains contain about 70-110 amino acids and are
classified into different categories (for example, variable or V,
and constant or C) according to their size and function. They have
a characteristic immunoglobulin fold in which two .beta. sheets
create a "sandwich" shape, held together by interactions between
conserved cysteines and other charged amino acids.
There are five types of mammalian Ig heavy chain denoted by
.alpha., .delta., .epsilon., .gamma., and .mu.. The type of heavy
chain present defines the isotype of antibody; these chains are
found in IgA, IgD, IgE, IgG, and IgM antibodies, respectively.
Distinct heavy chains differ in size and composition; .alpha. and
.gamma. contain approximately 450 amino acids and .delta.
approximately 500 amino acids, while .mu. and .epsilon. have
approximately 550 amino acids. Each heavy chain has two regions,
the constant region (C.sub.H) and the variable region (V.sub.H). In
one species, the constant region is essentially identical in all
antibodies of the same isotype, but differs in antibodies of
different isotypes. Heavy chains .gamma., .alpha. and .delta. have
a constant region composed of three tandem Ig domains, and a hinge
region for added flexibility; heavy chains .mu. and .epsilon. have
a constant region composed of four immunoglobulin domains. The
variable region of the heavy chain differs in antibodies produced
by different B cells, but is the same for all antibodies produced
by a single B cell or B cell clone. The variable region of each
heavy chain is approximately 110 amino acids long and is composed
of a single Ig domain.
In mammals, there are two types of immunoglobulin light chain
denoted by .lamda. and .kappa.. A light chain has two successive
domains: one constant domain (CL) and one variable domain (VL). The
approximate length of a light chain is 211 to 217 amino acids. Each
antibody contains two light chains that are always identical; only
one type of light chain, .kappa. or .lamda., is present per
antibody in mammals.
Although the general structure of all antibodies is very similar,
the unique property of a given antibody is determined by the
variable (V) regions, as detailed above. More specifically,
variable loops, three each the light (VL) and three on the heavy
(VH) chain, are responsible for binding to the antigen, i.e. for
its antigen specificity. These loops are referred to as the
Complementarity Determining Regions (CDRs). Because CDRs from both
VH and VL domains contribute to the antigen-binding site, it is the
combination of the heavy and the light chains, and not either
alone, that determines the final antigen specificity.
An "antibody fragment" contains at least one antigen binding
fragment as defined above, and exhibits essentially the same
function and specificity as the complete antibody of which the
fragment is derived from. Limited proteolytic digestion with papain
cleaves the Ig prototype into three fragments. Two identical amino
terminal fragments, each containing one entire L chain and about
half an H chain, are the antigen binding fragments (Fab). The third
fragment, similar in size but containing the carboxyl terminal half
of both heavy chains with their interchain disulfide bond, is the
crystalizable fragment (Fc). The Fc contains carbohydrates,
complement-binding, and FcR-binding sites. Limited pepsin digestion
yields a single F(ab')2 fragment containing both Fab pieces and the
hinge region, including the H--H interchain disulfide bond. F(ab')2
is divalent for antigen binding. The disulfide bond of F(ab')2 may
be cleaved in order to obtain Fab'. Moreover, the variable regions
of the heavy and light chains can be fused together to form a
single chain variable fragment (scFv).
Pharmaceutically acceptable salts are for example acid addition
salts and basic salts. Acid addition salts are e.g. HCl or HBr
salts. Basic salts are e.g. salts having a cation selected from
alkali or alkaline, e.g. Na+, or K+, or Ca2+, or an ammonium ion
N+(R1)(R2)(R3)(R4), wherein R1 to R4 independently of each other
mean: hydrogen, an optionally substituted C1-C6-alkyl group, an
optionally substituted C2-C6-alkenyl group, an optionally
substituted C6-C10-aryl group, or an optionally substituted
C6-C10-heteroaryl group. Further examples of pharmaceutically
acceptable salts are described in "Remington's Pharmaceutical
Sciences" 17. ed. Alfonso R. Gennaro (Ed.), Mark Publishing
Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia of
Pharmaceutical Technology.
Pharmaceutically acceptable solvates are for example hydrates.
Further scope of applicability of the present invention will become
apparent from the detailed description given hereinafter. However,
it should be understood that the detailed description and specific
examples, while indicating preferred embodiments of the invention,
are given by way of illustration only, since various changes and
modifications within the spirit and scope of the invention will
become apparent to those skilled in the art from this detailed
description.
BRIEF DESCRIPTION OF THE DRAWINGS
The present invention will become more fully understood from the
detailed description given hereinbelow and the accompanying
drawings which are given by way of illustration only, and thus, are
not limitive of the present invention, and wherein:
FIG. 1 is a schematic longitudinal section of a drug delivery
device.
DETAILED DESCRIPTION
FIG. 1 is a schematic longitudinal section of a drug delivery
device 1. The drug delivery device 1 comprises a drug container 2,
e.g. a syringe defining a cavity 3 for containing a drug. The
cavity is proximally delimited by a stopper 4 slidably arranged
within the container 2 so as to displace the drug from the cavity
through a discharge nozzle 5 arranged distally on the container 2.
The discharge nozzle 5 may be arranged as an injection needle or a
jet nozzle. The discharge nozzle 5 may be attached to the drug
container 2 by a nozzle connector 5.1 such as a needle hub.
The drug container 2 is retained within a case 6. The case 6
comprises a cylinder 7 whose end faces are closed by a rear cover 8
and a front cover 9. The front cover 9 has an aperture for allowing
the discharge nozzle 5 to extend from the case and/or to allow
insertion of the drug container 2 into the case 6. A front
retaining plate 10 is distally attached to the front cover 9
reducing the width of the aperture for fixing the drug container 2
in its axial position once it is inserted. The front retaining
plate 10 may be attached to the front cover by at least one screw
11.
The rear cover 8 comprises a container socket 8.2 having
essentially the same internal diameter as the outer diameter of the
drug container 2. The container socket 8.2 is axially aligned with
the drug container 2. In order to maintain alignments the rear
cover 8 and front cover 9 may be rotationally fixed to the cylinder
7, e.g. by gluing or screwing.
Inside the case 6 a magnet retainer 12 is arranged over the drug
container 2 and movable in an axial direction. The magnet retainer
12 holds at least one outer magnet 13 which may be arranged as a
ring magnet. An inner magnet 14 for interacting with the outer
magnet 13 is arranged within the drug container 2 proximally from
the stopper 4. The inner magnet 14 is preferably cylindrical.
A threaded bolt 15 is arranged in parallel with the drug container
2 within the case 6. The threaded bolt 15 engages the magnet
retainer 12 which has a corresponding screw thread such that the
magnet retainer 12 is translated in the axial direction on rotation
of the threaded bolt 15. A dosing handle 16 is attached to the
threaded bolt 15 and extends proximally from the rear cover 8 so as
to allow a user to grab, rotate and press it.
The threaded bolt 15 has two non-threaded sections 15.1, 15.2 at
its distal and proximal ends and a threaded section 15.3 in
between, wherein the non-threaded sections 15.1, 15.2 are axially
guided in respective guiding bores 8.1, 9.1 within the rear cover 8
and front cover 9 so as to allow some axial translation of the
threaded bolt 15 relative to the case 6, which may be limited by
the threaded section 15.3 of the threaded bolt 15 having a greater
diameter than the non-threaded sections 15.1, 15.2 or by a
respective collar on the threaded bolt with an increased diameter
or by the dosing handle 16 abutting the rear cover 8.
A tear-resistant, tightened cord 17 with low or no flexibility,
e.g. comprising steel and/or polyethylene and/or aramid fibres
connects the proximal face of the inner magnet 14 with the distal
face of the magnet retainer 12, wherein the cord 17 runs from the
inner magnet 14 in the proximal direction P through the container
socket 8.2 into a deviating point 18 in the rear cover 8, then back
in the distal direction D near the wall of the cylinder 7 and
through another deviating point 18 in the front cover 9 and
eventually again in the proximal direction P to the magnet retainer
12.
The inner magnet 14 is polarized with respect to the outer magnet
13 such that they attract each other and tend to arrive in a
relative rest position.
However, the length of the cord 17 is set so as to keep the inner
magnet 14 and the outer magnet 13 axially offset, i.e. a small
distance away from the rest position of the inner magnet 14 with
respect to the outer magnet 13. This offset keeps the cord 17
tight. Due to the low flexibility of the cord 17 and the magnetic
attraction between the magnets 13, 14 the relative axial offset
between the magnets 13, 14 is held constant. Thus, when the outer
magnet 13 is moved by a certain distance the inner magnet 14 moves
by the same distance thus allowing for high dose accuracy.
A dose to be delivered by the drug delivery device 1 may be set by
rotating the dosing handle 16 and hence the threaded bolt 15 which
consequently moves in the proximal direction P depending on the
number of rotations and/or angle of rotation and the pitch of the
threaded section 15.3. Thus, the distance, by which the corded bolt
15 can be depressed and hence the distance, by which the stopper 4
is shifted on depression of the dosing handle 16, is varied. The
stopper displacement is proportional to the delivered dose.
In the illustrated embodiment the threaded bolt 15 comprises a
right handed screw thread. Hence, when looking onto the dosing
handle 16 from the distal end the dose is set by rotating the
dosing handle 16 counter-clockwise. It goes without saying that the
corded bolt 15 could likewise comprise a left handed screw cord
such that the dose could be set by clockwise rotation.
After setting the intended dose the user may find a suitable
injection site and place the distal end of the drug delivery device
1 against the injection site thereby inserting the injection needle
5 into the injection site, if applicable. The user may then depress
the dosing handle 16 thereby advancing the threaded bolt 15 until
the displacement of the threaded bolt 15 is limited as described
above.
Advancing the threaded bolt 15 also advances the magnet retainer 12
with the outer magnet 13. Due to the magnetic attraction the inner
magnet 14 is also dragged in the distal direction D and thus
displaces the stopper 4 thereby delivering the set dose through the
discharge nozzle 5.
The operations of dose setting and delivery may be repeated until
the drug container 2 is empty.
Once the drug container 2 is empty it may be replaced by rotating
the dosing handle 16 in the clockwise sense until the inner magnet
14 is within the container socket 8.2. The front retaining plate 10
may then be loosened, the drug container 2 removed, a new one
inserted and the retaining plate 10 re-attached.
The cylinder 7 of the case 6 may likewise be integrally shaped with
the rear cover 8 and/or the front cover 9.
* * * * *